Androgen receptors (AR) are intracellular receptors that specifically bind androgens, such as testosterone and dihydrotestosterone, but are also known to be activated by growth factors, such as insulin-like growth factor-1 (IGF-1). The influence of testosterone on skeletal muscle protein synthesis is mediated by the AR. After an androgen binds to the AR, restructuring and dimerization of the proteins occurs forming an activated receptor complex, which translocates to the nucleus and binds to DNA, thereby activating androgen-specific gene expression in the nucleus.
Animal and clinical studies indicate that the AR signaling pathway is required for the appropriate development of skeletal muscles, as it regulates increases in lean muscle mass, muscle strength, and muscle protein synthesis. The importance of AR for muscle protein accretion has been shown, since muscle hypertrophy has been shown to be attenuated by AR blockade (Inoue K, Yamasaki S, Fushiki T, Okada Y, Sugimoto E. Androgen receptor antagonist suppresses exercise-induced hypertrophy of skeletal muscle. Eur J Appl Physiol Occup Physiol. 1994;69(1):88-91).
The physiological importance of AR in exercise-induced muscle hypertrophy has been investigated in a number of human and animal studies, most of which emphasize the importance of increasing the AR content (Deschenes M R, Maresh C M, Armstrong L E, Covault J, Kraemer W J, Crivello J F. Endurance and resistance expercise induce muscle fiber type specific responses in androgen binding capacity. J Steroid Biochem Mol. Biol. 1994 August; 50(3-4):175-9), in a muscle-fiber-specific manner. For example, resistance exercise elicits significant decreases in AR content of slow oxidative skeletal muscle fibers, and a significant increase in fast glycolytic skeletal muscle fibers.
In untrained men, a single bout of heavy resistance exercise has been shown to up-regulate AR mRNA 48 hours post-training (Bamman M M, Shipp J R, Jiang J, Gower B A, Hunter G R, Goodman A, McLaffert C L Jr, Urban R J. Mechanical load increases musvle IGF-I and androgen receptor mRNA concentrations in humans. Am J Physiol Endocrinol Metab. 2001 March; 280(3):E383-90). While, repeated resistance exercise, having 48 hours between sessions, has been shown to increase AR mRNA and protein expression (Willoughby D S, Taylor L. Effects of sequential bouts of resistance exercise on androgen receptor expression. Med Sci Sports Exerc. 2004 September; 36(9):1499-506). Such augmentation has been correlated with elevated serum testosterone levels and corresponded to significant increases in myofibrillar protein.
In trained individuals, high-volume, high-intensity resistance exercise appears to cause a decrease in AR protein content within 1 hour post-exercise (Ratamess N A, Kraemer W J, Volek J S, Maresh C M, Vanheest J L, Sharman M J, Rubin M R, French D N, Vescovi J D, Silvestre R, Hatfield D L, Fleck S J, Deschenes M R. Androgen receptor content following heavy resistance exercise in men. J Steroid Biochem Mol. Biol. 2005 January:93(1):35-42), almost certainly due to protein catabolism induced by exercise-related stress. However, this negative effect is mitigated by post-resistance exercise feeding, which has been shown to increase muscle AR content, resulting in increased testosterone tissue uptake and enhanced luteinizing hormone release, via feedback mechanisms. These observations provide a possible mechanism for increased protein synthesis following post-resistance exercise food intake.